Phosphatidic acid phosphatase, a key enzyme in the regulation of lipid synthesis.

PA2 phosphatase (PAP3; 3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) catalyzes the Mg2 -dependent dephosphorylation of PA, yielding DAG and Pi (Fig. 1) (1–3). In de novo lipid synthesis, the DAG generated from the PAP reaction is utilized for the synthesis of the phospholipids PE and PC via the Kennedy pathway and for the synthesis of TAG (Fig. 1) (3). The enzyme substrate PA is also used for phospholipid synthesis via CDP-DAG (Fig. 1) (1–3). In lipid signaling, PAP generates a pool of DAG used for protein kinase C activation, and by the nature of its reaction, it attenuates the signaling functions of PA (Fig. 1) (4–8). Thus, the regulation of PAP activity may govern the pathways by which phospholipids are synthesized and control the cellular contents of important signaling lipids. Recent genetic and biochemical studies in yeast and mammalian cells have revealed key roles that PAP plays in lipid metabolism and cell physiology.